Apparatus and methods for restoring tissue

ABSTRACT

An apparatus and methods for tissue restoration are provided. The apparatus may include a catheter shaft extending from a proximal end to a distal tip, the catheter shaft defining lumens including an inflation lumen and a light fiber lumen, a coated balloon positioned on a translucent distal segment of the catheter shaft proximal to the distal tip in fluid communication with the inflation lumen, the coated distal balloon comprising a translucent material and a coated material on an outer surface of the coated balloon, and a light fiber positioned in the catheter shaft in the light fiber lumen and extending through the translucent distal segment.

BACKGROUND Technical Field

The present disclosure generally relates to apparatus and methods torestore a vessel patency. More particularly, and without limitation, thedisclosed embodiments relate to catheters, and catheter systems tocreate a natural vessel scaffolding and restore vessel patency.

Background Description

Balloon catheters are used in a number of surgical applicationsincluding occluding blood flow either distally or proximally of atreatment site. The inflation of the balloon must be controlled in orderto avoid over-expansion or breakage of the balloon, which may rupture orotherwise damage the vessel. Percutaneous Transluminal Angioplasty(PTA), in which a balloon is used to open obstructed arteries, has beenwidely used to treat atherosclerotic lesions. However, this technique islimited by the vexing problems of re-occlusion and restenosis.Restenosis results from the excessive proliferation of smooth musclecell (SMC), and the rate of restenosis is above 20%. Thus, about one infive patients treated with PTA must be treated again within severalmonths.

Additionally, stenting is a popular treatment, in which a constrictedarteriosclerotic segment of the artery is mechanically expanded with theaid of a balloon catheter, followed by placement of a metallic stentwithin the vascular lumen to restore the flow of blood. Constriction orocclusion of the artery is problematic and can be itself, or cause, amajor health complication(s). Intraluminal placement of a metallic stenthas been found to result in the need for postoperative treatment in 20%to 30% of patients. One cause of this high frequency of requiredpostoperative treatment is vascular intimal hyperplasia within thevascular lumen resulting in lumen narrowing despite the stent beingplaced. In order to decrease in-stent restenosis, attempts have beenmade to design a stent of a type having a surface carrying arestenosis-inhibiting drug so that when the stent is placed in anartery, the drug is eluted in a controlled manner within the vascularlumen. Those attempts have led to commercialization of drug-elutingstents (hereinafter referred to as DES) utilizing various drugs such assirolimus (immunosuppressor) and paclitaxel (cytotoxic antineoplasticdrug). However, since those drugs have an effect of inhibiting theproliferation of vascular cells (endothelial cells and smooth musclecells) by acting on the cell cycle thereof, not only can the vascularintimal hyperplasia resulting from an excessive proliferation of thesmooth muscle cells be suppressed, but proliferation is also suppressedof endothelial cells once denuded during placement of the stent. Thiscan result in the adverse effect where the repair or treatment of theintima of a blood vessel becomes reduced. In view of the fact thatthrombosis tends to occur more easily at a site less covered withendothelial cells in the intima of a blood vessel, an antithromboticdrug must be administrated for a prolonged time, say, half a year or soand, notwithstanding this antithrombotic drug administration, a risk oflate thrombosis and restenosis will occur upon its discontinuance.

The technical problem addressed by the present disclosure is thereforeto overcome these prior art difficulties by creating devices providingfor controlled delivery of therapeutic agents to the surroundingtissues, propping a vessel open to a final shape, and functionalizingthe therapeutic agent within the tissue and forming a cast shape,permitting blood flow and restoring tissue function. The solution tothis technical problem is provided by the embodiments described hereinand characterized in the claims.

SUMMARY

The embodiments of the present disclosure include catheters, cathetersystems, and methods of forming a tissue scaffolding using cathetersystems. Advantageously, the exemplary embodiments allow for controlled,uniform delivery of therapeutic agents to the surrounding tissues,casting the tissue to a final shape, and functionalizing the therapeuticagent in the tissue, forming the cast shape and propping the vesselopen. The tissue may be a vessel wall of a vessel within thecardiovascular system.

According to embodiments of the present disclosure, an apparatus isprovided. The apparatus may include a catheter shaft extending from aproximal end to a distal tip and having a translucent distal segment,the catheter shaft defining lumens including an inflation lumen and alight fiber lumen. The apparatus may further include a coated balloonpositioned on the distal segment proximal to the distal tip in fluidcommunication with the inflation lumen, the coated distal ballooncomprising a translucent material and a coated material on an outersurface of the coated balloon. The apparatus may also include a lightfiber positioned in the catheter shaft in the light fiber lumen andextending through the distal segment.

In some embodiments, the inflation lumen provides an inflation fluid tothe coated balloon, and a pressure of the inflation fluid in the coatedballoon causes the coated balloon to expand into an expanded state.

In some embodiments, the coated material is a Natural VascularScaffolding treatment compound. The Natural Vascular Scaffoldingcompound may be light activated.

In some embodiments, the translucent material of the distal segment andthe coated balloon is transparent. The light fiber may provide lightactivation through the distal segment and the coated balloon. The coatedballoon may include material that conforms to the morphology of thevessel wall. The catheter shaft may be shielded along the length of thecatheter shaft until the distal segment, allowing light transmission outof the distal segment and the coated balloon.

In some embodiments, the coated balloon has a compressed position thatprotects the coated material when the catheter shaft is guided to atarget area of the vessel. The coated balloon may contact a vessel wallin a target area and the coated material transfers from the outersurface of the coated balloon to the target area. The catheter shaft mayfurther define a guidewire lumen concentric with the catheter shaft. Thelight fiber lumen may extend to an opening in the distal tip, and thelight fiber lumen is configured to receive a cooling agent that passesthrough the light fiber lumen and exits the light fiber through theopening in the distal tip.

According to another embodiment of the present disclosure, a method oftissue restoration in a blood vessel of a subject is provided. Themethod may include providing a catheter into the blood vessel. Thecatheter may include a catheter shaft extending from a proximal end to adistal tip and having a translucent distal segment, the catheter shaftdefining lumens including an inflation lumen and a light fiber lumen.The apparatus may further include a coated balloon positioned on thedistal segment proximal to the distal tip in fluid communication withthe inflation lumen, the coated distal balloon comprising a translucentmaterial and a coated material on an outer surface of the coatedballoon. The apparatus may also include a light fiber positioned in thecatheter shaft in the light fiber lumen and extending through the distalsegment. The method may further include inflating the coated balloon toa predetermined pressure for a first predetermined amount of time, andactivating a light source connected to the light fiber for a secondpredetermined amount of time after the first predetermined amount oftime has completed, while keeping the coated balloon inflated, therebyproviding light transmission through the distal segment and the coatedballoon to activate the drug in the treatment area.

In some embodiments, the coated balloon is coated with a NaturalVascular Scaffolding treatment compound, the Natural VascularScaffolding compound is light activated. The light fiber may providelight activation through the distal segment and the coated balloon. Thecatheter shaft may be shielded along the length of the catheter shaftuntil the distal segment, thereby providing light transmission out ofthe distal segment and the coated balloon.

According to another embodiment of the present disclosure, an apparatusis provided. The apparatus may include a catheter shaft extending from aproximal end to a distal tip and having a translucent distal segment,the catheter shaft defining lumens including an inflation lumen and alight fiber lumen, a coated balloon positioned on the distal segmentproximal to the distal tip in fluid communication with the inflationlumen, the coated distal balloon comprising a translucent material and acoated material on an outer surface of the coated balloon, and a lightfiber positioned in the catheter shaft in the light fiber lumen andextending through the translucent distal segment. The catheter shaft maybe shielded along the length of the catheter shaft until the distalsegment, providing light transmission out of the distal segment and thecoated balloon and the coated material is a light-activated treatmentcompound.

Additional features and advantages of the disclosed embodiments will beset forth in part in the description that follows, and in part will beobvious from the description, or may be learned by practice of thedisclosed embodiments. The features and advantages of the disclosedembodiments will be realized and attained by the elements andcombinations particularly pointed out in the appended claims.

It is to be understood that both the foregoing general description andthe following detailed description are examples and explanatory only andare not restrictive of the disclosed embodiments as claimed.

The accompanying drawings constitute a part of this specification. Thedrawings illustrate several embodiments of the present disclosure and,together with the description, serve to explain the principles of thedisclosed embodiments as set forth in the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevational view of an exemplary apparatus including acatheter, according to embodiments of the present disclosure.

FIG. 2A is a side elevational view of a distal portion of the catheterof FIG. 1 .

FIG. 2B is a perspective partial section view of the exemplary catheterof FIG. 2A.

FIG. 3 is a side elevational view of a proximal portion of the catheterof FIG. 1 .

FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. 2A.

FIG. 5A is a side elevational view of a distal portion of anotherexemplary catheter according to embodiments of the present disclosure.

FIG. 5B is a perspective partial section view of the exemplary catheterof FIG. 5A.

FIG. 6 is a side elevational view of a proximal portion of the catheterof FIG. 5A.

FIG. 7 is a cross-sectional view taken along line 7-7 of FIG. 5A.

DETAILED DESCRIPTION

Reference will now be made in detail to embodiments and aspects of thepresent disclosure, examples of which are illustrated in theaccompanying drawings. Where possible, the same reference numbers willbe used throughout the drawings to refer to the same or like parts.

FIG. 1 illustrates an apparatus 100 in accordance with an embodiment ofthis disclosure. The apparatus 100 having a catheter shaft 104 thatextends from a proximal end 106 to a distal tip 110 of the apparatus100. The apparatus 100 may be configured for longitudinal movement andpositioning within a vessel (e.g. blood vessel) of a subject. In someembodiments, the apparatus 100 may be configured for treatment of anarea of the vessel. In some embodiments, the apparatus 100 may occludethe vessel, while in other embodiments the apparatus may not occlude thevessel. For example, the apparatus 100 may be configured for delivery ofa drug to an area of the vessel occupied by the apparatus 100 which mayform and cast a shape in the vessel, as will be described in more detailbelow.

The apparatus 100 may include a proximal end connector 114, shown inmore detail at FIG. 3 , positioned at the proximal end of the apparatus100, and the catheter shaft 104 may extend in a distal directiontherefrom. The catheter shaft 104 may define a plurality of lumens thatare accessible via a plurality of ports 115 of the proximal endconnector 114. The plurality of ports 115 may be configured to engagewith external sources desirable to communicate with the plurality oflumens. The ports may engage with external sources via a variety ofconnection mechanisms, including, but not limited to, syringes,over-molding, quick-disconnect connectors, latched connections, barbedconnections, keyed connections, threaded connections, or any othersuitable mechanism for connecting one of the plurality of ports to anexternal source. Non-limiting examples of external sources may includeinflation sources (e.g. saline solutions), gaseous sources, treatmentsources (e.g. medication, drugs, or any desirable treatment agentsdiscussed further below), light sources, among others. In someembodiments, apparatus 100 can be used with a guide wire (not shown),via guide wire lumen 164 (see FIG. 4 ), to assist in guiding thecatheter shaft 104 to the target area of the vessel.

FIGS. 1-4 illustrate the apparatus 100 may include a coated balloon 120positioned over a distal segment 130 of the catheter shaft 104 proximalto the distal tip 110. In some embodiments, the coated balloon 120 maybe proximally offset from the distal tip 110 a distance between 0 mm and1 mm, 0 mm and 2 mm, 0 mm and 3 mm, 0 mm and 10 mm, or 0 and 50 mm. Thecoated balloon 120 may take any shape suitable for supporting a wall ofa blood vessel or other hollow body structure of the subject when thecompliant or semi-compliant balloon is inflated. For example, the coatedballoon 120 may expand into a cylindrical shape surrounding the distalsegment 130 of the catheter shaft 104. The cylindrical shape may begradually tapered inward at a proximal end and a distal end of thecoated balloon 120, thereby providing a gradually tapered proximal endand distal end of the coated balloon 120 that taper into contact withand become flush with the catheter shaft 104.

Non-limiting examples of shapes the inflated coated balloon 120 may forminclude a cylindrical shape, football-shaped, spherical, ellipsoidal, ormay be selectively deformable in symmetric or asymmetric shapes so as tolimit the potential difference in the treated vessel shape and theuntreated vessel shape reducing edge effects common between two surfacesof different stiffness as found in metal stents. The force exertedagainst a vessel interior by coated balloon 120 may be strong enough toscaffold the vessel wall with the apparatus 100 held in a stationaryposition within the vessel or other hollow body structure. However, theforce is not so great as to damage the interior surface of the vessel orother hollow body structure. The coated balloon 120 may be substantiallytranslucent.

The apparatus 100 may include a plurality of connectors 115 positionedproximally to the proximal end connector 114. For example, the coatedballoon 120 may be terminated at the proximal end 106 with a connectorcapable of receiving an inflation source. In some embodiments, theconnector may be a luer configuration. A center lumen (discussed in moredetail below), may be terminated at the proximal end with a connectorcapable of receiving a fluid source for clearing the lumen from theproximal termination to outside the distal tip, and in some embodimentsmay include a luer configuration. The center lumen may also accommodatea guidewire for tracking the catheter apparatus to the desiredanatomical location. As discussed in more detail below, the apparatus100 may also include light fibers that may be terminated at the proximalend with an adaptor capable of connecting with a light source. Eachlight fiber may terminate with a separate and distinct adaptor or eachlight fiber may share an adaptor to a light source. The light fibers maybe integrated into the apparatus 100.

The materials of the apparatus 100 may be biocompatible. The cathetershaft 104 may include material that is extrudable and capable ofsustaining lumen integrity. The distal segment 130 of the catheter shaft104 is substantially translucent to allow light transmission from lightfibers. The catheter shaft 104 material is rigid enough to track over aguidewire and soft enough to be atraumatic. The catheter shaft 104 maybe made of materials including, but not limited to polymers, natural orsynthetic rubber, metal and plastic or combinations thereof, nylon,polyether block amide (PEBA), nylon/PEBA blend, thermoplasticcopolyester (TPC), a non-limiting example may be HYTREL® (available fromDupont de Nemours, Inc. of Wilmington, Del.), and polyethylene. Theshaft materials can be selected so as to maximize column strength to thelongitudinal length of the shaft. Further, the shaft materials can bebraided, so as to provide sufficient column strength. The shaftmaterials can also be selected so as to allow the device to movesmoothly along a guide wire. The catheter shaft 104 can also be providedwith a lubricious coating as well as antimicrobial and antithrombogeniccoatings. The shaft materials should be selected so as not to interferewith the efficacy of the agent to be delivered or collected. Thisinterference may take the form of absorbing the agent, adhering to theagent or altering the agent in any way. The catheter shaft 104 of thepresent disclosure may be between about 2-16 French units (“Fr.” whereone French equals ⅓ of a millimeter, or about 0.013 inches). Thecatheter shafts to be used in coronary arteries may be between about 3-5Fr. in diameter, and more specifically may be 3 Fr. The catheter shaftsto be used in peripheral vessels may be between about 5-8 Fr. indiameter, and more specifically 5 Fr. The catheter shafts to be used inthe aorta may be between about 8-16 Fr. in diameter, and morespecifically 12 Fr.

The coated balloon 120 may be substantially translucent permitting lightfrom light fibers to be transmitted substantially beyond the inflateddiameter of the coated balloon 120. The coated balloon 120 may becompliant such that the material conforms substantially to a vessel'smorphology. The coated balloon 120 material may be elastic, capable ofelastically conforming substantially to a vessel's morphology therebyproviding optimal drug delivery in a non-dilating and non-traumaticmanner. The apparatus 100 may not cause any further trauma (e.g. traumacaused by atherectomy or percutaneous transluminal angioplasty “PTA” orvessel preparation methods) to the vessel to promote optimal healing.

FIGS. 2A and 2B illustrate the coated balloon 120 that may be coatedwith one or more drugs, e.g. with Natural Vascular Scaffolding (NVS)compound, which may be activated by light as discussed further below.The expansion of the coated balloon 120 may shape the treatment area(e.g. vessel) as desired and may provide the one or more drugs (e.g.NVS) coated on the external surface of the coated balloon 120 to thetreatment area, as described in more detail below.

The coated balloon 120 may be expandable from a folded or compressedposition or orientation to an expanded position or orientation (FIG. 4). In some embodiments, the coated balloon 120 may be in a compressedposition, which may be a folded configuration, when the catheter shaft104 is guided to the target area of the vessel. The compressed or foldedconfiguration may protect the coated material on the outside surface ofthe coated balloon 120 when the catheter shaft 104 is guided to a targetarea of the vessel. When the coated balloon 120 is positioned in thetarget area, the coated balloon 120 may be inflated into an expandedposition.

The coated balloon 120 may include marker bands 122 positioned at aproximal end and a distal end of the coated balloon 120. The markerbands 122 may allow for precise location tracking of the coated balloon120 during a procedure such that a user (e.g. a surgeon) may be able toreadily locate the coated balloon 120 within an imaging system such asangiography. In some embodiments, the marker bands 120 may be radiopaquegold or platinum bands that are integrated into the apparatus 100.

In some embodiments, the light fiber 140 may be integrated into theapparatus 100. As used herein, the term “integrated” may refer to thelight fiber being over molded into the apparatus 100 such that the lightfiber becomes a non-interchangeable element of the apparatus 100. Inother embodiments, as will be described below, the light fiber 140 maybe removeable. In some embodiments, the light fiber may be integratedinto the apparatus 100 at the time of manufacture. In other embodiments,the light fiber may be integrated into the apparatus 100 in a catheterlab during a clinical preparation process.

The light fiber 140 may be positioned in the catheter shaft 104 andextend through the distal segment 130. The light fiber 140 may transmitlight through the distal segment 130 and the coated balloon 120. Thelight fiber 140 may be connected to the proximal end connector 114 andmay have proximal ends that connect to a light fiber activation sourcevia at least one of the plurality of ports 115. In some embodiments, thelight fiber 140 may be configured to transmit light at a wavelength of375 nanometers (nm) to 475 nm, and more specifically 450 nm thattransmits through the distal segment 130 and the coated balloon 120. Thelight fiber 140 may emit light outside of the ultraviolet (UV) range of10 nm to 400 nm. In some embodiments, the light fiber 140 may bepositioned in the light fiber lumen 158, and the light fiber 140 may becovered or shielded along the length of the catheter shaft 104 so thatlight is only transmitted out of the distal segment 130 and the coatedballoon 120.

In some embodiments, the light fiber 140 may be made from plastic coreand cladding. The refractive index of the core is high. The refractiveindex of the cladding is low. A non-limiting example of the corematerial may be polymethyl methacrylate (PMMA). A non-limiting exampleof the cladding may be a silicone material. The light source may controlthe wavelength and supplied power of the light fibers 140. The patternof the breaks in the cladding of the light fiber ensure uniform powerdistribution to the vessel wall. Longer lengths have a different patternthan shorter lengths. The distal lengths of cladding breaks are matchedto the length of the balloons.

FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. 2 showinga plurality of lumens within the assembly 100, according to anembodiment of this disclosure. The catheter shaft 104 may have anoutside diameter and outside surface 130. The catheter shaft 104 mayhave an inside configuration of three distinct and separate lumens,extending from the proximal end 106 to the distal tip 110.

The coated balloon 120 may be in fluid communication with an inflationlumen 150. The inflation lumen 150 may extend through the catheter shaft104 and have an input at one of the plurality of ports 115 of theproximal end connector 114. Fluid communication between the coatedballoon 120 and the inflation source via the inflation lumen 150 maycause the coated balloon 120 to selectively fill and expand.

A light fiber lumen 158 may be provided. A light fiber lumen may bepositioned in the catheter shaft 104 to receive one or more lightfibers, and the light fiber lumen 158 may extend from the proximal end106 into the distal segment 130. In another exemplary embodiment, thecatheter shaft 104 may include a plurality of light fiber lumens.

In some embodiments, the light fiber lumen 158 may extend from theproximal end 106 to the distal tip 110 and may include an opening ateach of the proximal end 106 and the distal tip 110. The light fiberlumen 158 may be configured to receive a cooling supply from theproximal end that may communicate a cooling agent (e.g. a fluid such asa saline solution), and the opening at the distal tip 110 may allow thecooling agent to pass through the light fiber lumen 158 and exit throughthe opening at the distal tip 110 of the light fiber lumen 158. In suchembodiments, the cooling agent passing through the light fiber lumen 158may surround the light fiber 140 and provide temperature regulation tothe light fiber 140.

A guidewire lumen 164 may also be provided. A guidewire lumen may beconcentric with the catheter shaft outside diameter and may be arrangedin the catheter shaft 104, from the proximal end 106 through the distaltip 110. The guidewire lumen 164 may accommodate a guidewire to aid theplacement of the apparatus 100 to a desired anatomical positioncommunicating with the proximal end and distal tip. The guidewire may beseparate and distinct from the apparatus 100 and extend proximallybeyond the proximal end and distally beyond the distal tip of thecatheter shaft. The guidewire lumen 164 is located concentric with thecatheter outer diameter; the catheter shaft is oriented concentricallywith the guidewire permitting the catheter shaft 104 to follow theguidewire without favoring one side of the catheter shaft 104 orwhipping from side to side. The guidewire may remain in the guidewirelumen 104 maintaining anatomical position during the activation of thelight fibers.

As shown, the catheter shaft 104 may a three-lumen extrusion of theinflation lumen 150, the light fiber lumen 158 and the guidewire lumen164. The guidewire lumen 164 may be concentrically positioned within thecatheter shaft 104 between the inflation lumen 150 and the light fiberlumen 158. The inflation lumen 150 and the light fiber lumen 158 mayhave a semi-circular or hemi-circular cross-sectional shape and may incombination surround the guidewire lumen 164 that is centrallypositioned between the inflation lumen 150 and the light fiber lumen158.

In some embodiments, the apparatus 100 may include a two-lumen extrusioninstead of the three-lumen extrusion shown in FIG. 4 . In such anembodiment, one lumen may be configured to receive a guidewire and theother lumen may be configured to receive a light fiber and be connectedto an inflation source so that the inflation source can fluidicallycommunicate with the coated balloon 120.

FIGS. 5A to 7 show another embodiment of an apparatus 200 having acoated balloon 220 with a catheter shaft 204 that receives a light fiber240 that is removeable. The coated balloon 220 may have the same orsimilar features to coated balloon 120 described above. The apparatus200 may share many of the same components and features of apparatus 100described above.

The coated balloon 220 is positioned over a distal segment 230 of thecatheter shaft 204 proximal to the distal tip 210. In some embodiments,the coated balloon 220 may be proximally offset from the distal tip 110a distance between 0 mm and 1 mm, 0 mm and 2 mm, 0 mm and 3 mm, 0 mm and10 mm, or 0 and 50 mm. The coated balloon 220 may take any shapesuitable for supporting a wall of a blood vessel or other hollow bodystructure of the subject when the compliant or semi-compliant balloon isinflated, as described above in reference to the coated balloon 220.

The coated balloon 220 may include marker bands 222 positioned at aproximal end and a distal end of the coated balloon 220. The markerbands 222 may allow for precise location tracking of the coated balloon220 during a procedure such that a user (e.g. a surgeon) may be able toreadily locate the coated balloon 220 within an imaging system. In someembodiments, the marker bands 220 may be radiopaque gold or platinumbands that are integrated into the apparatus 200.

The apparatus 200 may include a proximal end connector 214, shown inmore detail at FIG. 6 , positioned at the proximal end of the apparatus200, and the catheter shaft 204 may extend in a distal directiontherefrom. The catheter shaft 204 may define lumens that are accessiblevia one or more of ports 215 of the proximal end connector 214. Theports 215 may be configured to engage with external sources desirable tocommunicate with the plurality of lumens. The ports may engage withexternal sources via a variety of connection mechanisms, including, butnot limited to, syringes, over-molding, quick-disconnect connectors,latched connections, barbed connections, keyed connections, threadedconnections, or any other suitable mechanism for connecting one of theplurality of ports to an external source. Non-limiting examples ofexternal sources may include inflation sources (e.g. saline solutions),gaseous sources, treatment sources (e.g. medication, drugs, or anydesirable treatment agents discussed further below), light sources,among others. In some embodiments, apparatus 200 can be used with aguide wire (not shown), via guide wire lumen 264 (see FIG. 7 ), toassist in guiding the catheter shaft 204 to the target area of thevessel.

FIG. 7 is a cross-sectional view taken along line 7 to 7 of FIG. 5Ashowing the lumens within the assembly 200, according to an embodimentof this disclosure. The catheter shaft 104 may have an insideconfiguration of two distinct and separate lumens, extending from theproximal end 206 to the distal tip 210.

The coated balloon 220 may be in fluid communication with an inflationlumen 250. The inflation lumen 250 may extend through the catheter shaft204 and have an input at one of the ports 215 of the proximal endconnector 214. Fluid communication between the coated balloon 220 andthe inflation source via the inflation lumen 250 may cause the coatedballoon 220 to selectively fill and expand.

A light fiber lumen 264 may be positioned in the catheter shaft 204 toreceive light fibers and guide wires, and the light fiber lumen 264 mayextend from the proximal end 206 into the distal segment 230. The lightfiber lumen 264 may be concentric with the catheter shaft 204 and theinflation lumen 250 and may be arranged in the catheter shaft 204, fromthe proximal end 206 through the distal tip 210. The light fiber lumen264 may accommodate a guidewire to aid the placement of the apparatus200 to a desired anatomical position communicating with the proximal endand distal tip. The guidewire may be separate and distinct from theapparatus 200 and extend proximally beyond the proximal end and distallybeyond the distal tip of the catheter shaft. The guidewire lumen 264 islocated concentric with the catheter outer diameter; the catheter shaftis oriented concentrically with the guidewire permitting the cathetershaft 204 to follow the guidewire without favoring one side of thecatheter shaft 204 or whipping from side to side. The guidewire mayremain in the light fiber lumen 264 maintaining anatomical positionduring the activation of the light fibers.

The light fiber may be removeable and may be inserted through the lightfiber lumen 264 to be positioned in the catheter shaft 204 and extendthrough the distal segment 230. The light fiber may transmit lightthrough the distal segment 230 and the coated balloon 220. The lightfiber may be connected to the proximal end connector 214 and may haveproximal ends that connect to a light fiber activation source via atleast one of the ports 215. In some embodiments, the light fiber may beconfigured to transmit light at a wavelength of 375 nanometers (nm) to475 nm, and more specifically 450 nm that transmits through the distalsegment 230 and the coated balloon 220. The light fiber may emit lightoutside of the ultraviolet (UV) range of 10 nm to 400 nm. In someembodiments, the light fiber may be positioned in the light fiber lumen264, and the light fiber may be covered or shielded along the length ofthe catheter shaft 204 so that light is only transmitted out of thedistal segment 230 and the coated balloon 220.

Now that the components of each apparatus 100, 200 have been describedin detail, the methods associated with both apparatuses 100 and 200 canbe appreciated. The target area for a delivery of drug source may be avessel of the cardiovascular system. In some embodiments, the targetarea may be first prepared by percutaneous transluminal angioplasty(PTA) or atherectomy to displace or remove damaged vessel cellulardebris. The catheter apparatus 100, 200 may not be intended to replacePTA; the functional pressure of the coated balloon 120, 220 is onlysufficient to prop open the vessel during drug functionalization. Thecoated balloon 120, 220 may be inflated which into contact with thevessel wall in order to uniformly deliver the coated drug to the vesselwall. While in this vessel supported position, a light source may besupplied to the light fibers 140 in the catheter shaft 104, 204 fortransmittance through the catheter shaft 104, 204, through the coatedballoon 120, 220 and into the vessel wall.

An embodiment of this disclosure provides an exemplary method of tissuerestoration in a blood vessel of a subject. The method may includeproviding an apparatus (e.g. apparatus 100, 200) and preparing theapparatus for a clinical procedure, which may include sterilizing theapparatus and connecting the light fiber to the light source. The methodmay further include advancing the apparatus to the treatment site over aguidewire using angiography for visualization and aligning the markerbands with the desired treatment site. Subsequently, the balloon may beinflated to a desired pressure based on a sizing chart for the treatmentarea (e.g. based on the diameter of the treatment vessel) and maintainthe inflation of the balloon a predetermined amount of time (e.g. one tothree minutes), allowing the drug to transfer into the wall of theartery.

The method may further include, while the balloon remains inflated,turning on the light source for a predetermined amount of time (e.g. oneto three minutes), transmitting light down the light fiber and allowingthe light to activate the drug that has been transported into theartery. Once complete, the balloon may be deflated and removed.

Another embodiment of this disclosure includes an exemplary method oftissue restoration in a blood vessel of a subject. The method mayinclude providing an apparatus (e.g. apparatus 100, 200) and preparingthe apparatus for a clinical procedure, which may include sterilizingthe apparatus and connecting the light fiber to the light source. Themethod may further include advancing the apparatus to the treatment siteover a guidewire using angiography for visualization and aligning themarker bands with the desired treatment site. Subsequently, the balloonmay be inflated to a desired pressure based on a sizing chart for thetreatment area (e.g. based on the diameter of the treatment vessel) andmaintain the inflation of the balloon a predetermined amount of time(e.g. one to three minutes), allowing the drug to transfer into the wallof the artery.

The method may further include, while the balloon remains inflated,removing the guidewire and placing the light fiber down the guidewirelumen. Once the light fiber is in position, the method includes turningon the light source for a predetermined amount of time (e.g. one tothree minutes), transmitting light down the light fiber and allowing thelight to activate the drug that has been transported into the artery.Once complete, the light fiber may be removed, and the guidewire may beplaced back into the apparatus so that the deflated balloon may beremoved.

In some embodiments, the drug is not cured or activated, but the drug isfunctionalized to cross-link with tissue proteins. The tissue proteins,the drug, and the light may be present to create a therapeutic effect.The functionalizing of the drug may not be time dependent, butinstantaneous or nearly so, dependent on wavelength alone at the properintensity. The light power compensates for losses through the lightfiber, balloon, and tissue wall and may be balanced to avoid heatbuildup during therapy. Additionally or alternatively, thefunctionalizing of the drug may be correlated to the light power that isoscillated, pulsed, or is off-duty cycled where the light power is onfor a period of time and off for another period of time. In someembodiments, the duty cycle may be 10%, which means the light power ison for 10% of the time and off for 90% of the time. In otherembodiments, the duty cycle may be 20%, 30%, 40%, 50%, 60%, 70%, 80%, or90%.

Additionally, therapeutic agents useful with the device of the presentdisclosure include any one of or a combination of several agents whichare gas, liquid, suspensions, emulsions, or solids, which may bedelivered or collected from the vessel for therapeutic or diagnosticpurposes. Therapeutic agents may include biologically active substances,or substances capable of eliciting a biological response, including, butnot limited to endogenous substances (growth factors or cytokines,including, but not limited to basic fibroblast growth factor, acidicfibroblast growth factor, vascular endothelial growth factor, angiogenicfactors, microRNA), viral vectors, DNA capable of expressing proteins,sustained release polymers, and unmodified or modified cells.Therapeutic agents may include angiogenic agents which induce theformation of new blood vessels. Therapeutic agents may also includeanti-stenosis or anti-restenosis agents which are used to treat thenarrowing of blood vessel walls. Therapeutic agents may includelight-activated agents such as light-activated anti-stenosis orlight-activated anti-restenosis agents that may be used to treat thenarrowing of blood vessel walls.

Accordingly, apparatus 100 is multifunctional, providing drug deliverycontrol in open and closed positions, and propping open a vessel wallforming a shape during drug functionalizing with a light source of aspecific wavelength outside of the ultraviolet (UV) range (10 nm to 400nm).

Accordingly, the apparatus and methods described herein provide thedelivery of NVS to a treatment area (e.g. a vessel) and providerestoration to that treatment area using the apparatus or according tothe methods described above. The apparatus and method described aboveprovide concurrently treating the vessel with one or more drugs (e.g.with Paclitaxel and NVS) with minimal loss to other vessels, scaffoldingand casting the vessel, and light activation of the one or more drugsdelivered to the treatment area. These advantages can be accomplishedutilizing the apparatus and methods described herein.

According to embodiments of the present disclosure, the NVS compound mayinclude dimeric naphthalmides as described in U.S. Pat. No. 6,410,505B2, and U.S. Provisional Patent Application No. 62/785,477. For example,a dimeric naphthalimide compound,2,2′-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(6-((2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione),also known as 10-8-10 dimer,6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-2-[2-[2-[2-[6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-1,3-dioxobenzo[de]isoquinolin-2-yl]ethoxy]ethoxy]ethyl]benzo[de]isoquinoline-1,3-dione;2,2′-[1,2-ethanediylbix(oxy-2,1-ethanediyl)]bis[6-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione];and 1H-benz[de]isoquinoline-1,3(2H)-dione,2,2′-[1,2-ethanediylbis(oxy-2,1-ethanediyl)]bis[6-[[2-[2-(2-aminoethoxy)ethoxy]ethyl]amino]-(9Cl),and herein referred to as Compound of Formula (I), has been disclosed.Id.

The foregoing description has been presented for purposes ofillustration. It is not exhaustive and is not limited to precise formsor embodiments disclosed. Modifications and adaptations of theembodiments will be apparent from consideration of the specification andpractice of the disclosed embodiments. For example, the describedimplementations include hardware and software, but systems and methodsconsistent with the present disclosure can be implemented as hardwarealone. In addition, while certain components have been described asbeing coupled to one another, such components may be integrated with oneanother or distributed in any suitable fashion.

Moreover, while illustrative embodiments have been described herein, thescope includes any and all embodiments having equivalent elements,modifications, omissions, combinations (e.g., of aspects across variousembodiments), adaptations and/or alterations based on the presentdisclosure. The elements in the claims are to be interpreted broadlybased on the language employed in the claims and not limited to examplesdescribed in the present specification or during the prosecution of theapplication, which examples are to be construed as nonexclusive.Further, the steps of the disclosed methods can be modified in anymanner, including reordering steps and/or inserting or deleting steps.

The features and advantages of the disclosure are apparent from thedetailed specification, and thus, it is intended that the appendedclaims cover all systems and methods falling within the true spirit andscope of the disclosure. As used herein, the indefinite articles “a” and“an” mean “one or more.” Similarly, the use of a plural term does notnecessarily denote a plurality unless it is unambiguous in the givencontext. Words such as “and” or “or” mean “and/or” unless specificallydirected otherwise. Further, since numerous modifications and variationswill readily occur from studying the present disclosure, it is notdesired to limit the disclosure to the exact construction and operationillustrated and described, and accordingly, all suitable modificationsand equivalents may be resorted to, falling within the scope of thedisclosure (e.g., slitted apertures, apertures, perforations may be usedinterchangeably maintaining the true scope of the embodiments)

Other embodiments will be apparent from consideration of thespecification and practice of the embodiments disclosed herein. It isintended that the specification and examples be considered as exampleonly, with a true scope and spirit of the disclosed embodiments beingindicated by the following claims.

1.-20. (canceled)
 21. A method for natural vessel scaffolding in apatient comprising: providing a catheter device, the device having: acatheter shaft extending from a proximal end to a distal tip and havinga translucent distal segment, the catheter shaft defining lumensincluding an inflation lumen and a light fiber lumen; a coated balloonpositioned on the distal segment proximal to the distal tip in fluidcommunication with the inflation lumen, the coated distal ballooncomprising a translucent material and a coated material on an outersurface of the coated balloon; and a light fiber positioned in thecatheter shaft in the light fiber lumen and extending through the distalsegment; positioning the coated balloon to at least partially contact avessel wall in an expanded state; expanding the coated balloon; andtransferring a therapeutically effective quantity of the coated materialfrom the outer surface of the coated balloon to the vessel wall.
 22. Themethod of claim 21, wherein the expanding step further comprisesproviding an inflation fluid through the inflation lumen to the coatedballoon, and a pressure of the inflation fluid in the coated ballooncauses the coated balloon to expand into an expanded state.
 23. Themethod of claim 21, wherein the coated material is a Natural VascularScaffolding treatment compound.
 24. The method of claim 23, wherein theNatural Vascular Scaffolding compound is light activated.
 25. The methodof claim 21 wherein the translucent material of the distal segment andthe coated balloon is transparent.
 26. The method of claim 21 furthercomprising the step of light activating the transferred material withthe light fiber.
 27. The method of claim 21, wherein the expanding stepfurther comprises conforming the coated material on the coated balloonto the morphology of the vessel wall.
 28. The method of claim 21,wherein the catheter shaft is shielded along the length of the cathetershaft until the distal segment, allowing light transmission out of thedistal segment and the coated balloon.
 29. The method of claim 21,wherein the positioning step further comprises keeping the coatedballoon in a compressed position that protects the coated material whenthe catheter shaft is guided to a target area of the vessel.
 30. Themethod of claim 21, wherein the catheter shaft further defines aguidewire lumen concentric with the catheter shaft.
 31. The method ofclaim 21, wherein the light fiber lumen extends to an opening in thedistal tip; further comprising the step of providing a cooling agentthrough the light fiber lumen that exits the light fiber through theopening in the distal tip.
 32. A method for restoring tissue in a mammalcomprising: providing a catheter device, the device having: a cathetershaft extending from a proximal end to a distal tip and having atranslucent distal segment, the catheter shaft defining lumens includingan inflation lumen and a light fiber lumen; a coated balloon positionedon the distal segment proximal to the distal tip in fluid communicationwith the inflation lumen, the coated distal balloon comprising atranslucent material and a coated material on an outer surface of thecoated balloon; and a light fiber positioned in the catheter shaft inthe light fiber lumen and extending through the distal segment;identifying target tissue in the mammal for treatment; positioning thecoated balloon to at least partially contact target tissue in anexpanded state; expanding the coated balloon; and transferring atherapeutically effective quantity of the coated material from the outersurface of the coated balloon to the vessel wall.
 33. The method ofclaim 32, wherein the expanding step further comprises providing aninflation fluid through the inflation lumen to the coated balloon, and apressure of the inflation fluid in the coated balloon causes the coatedballoon to expand into an expanded state.
 34. The method of claim 32,wherein the coated material is a Natural Vascular Scaffolding treatmentcompound.
 35. The method of claim 34, wherein the Natural VascularScaffolding compound is light activated.
 36. The method of claim 32wherein the translucent material of the distal segment and the coatedballoon is transparent.
 37. The method of claim 32 further comprisingthe step of light activating the transferred material with the lightfiber.
 38. The method of claim 32, wherein the expanding step furthercomprises conforming the coated material on the coated balloon to themorphology of the target tissue.
 39. The method of claim 32, wherein thecatheter shaft is shielded along the length of the catheter shaft untilthe distal segment, allowing light transmission out of the distalsegment and the coated balloon.
 40. The method of claim 32, wherein thepositioning step further comprises keeping the coated balloon in acompressed position that protects the coated material when the cathetershaft is guided to a target area of the vessel.
 41. The method of claim32, wherein the catheter shaft further defines a guidewire lumenconcentric with the catheter shaft.
 42. The method of claim 32, whereinthe light fiber lumen extends to an opening in the distal tip; furthercomprising the step of providing a cooling agent through the light fiberlumen that exits the light fiber through the opening in the distal tip.